Coffee consumption during pregnancy increases the risk of preeclampsia in rats by inhibiting 2-methoxyestradiol production.

Preeclampsia (PE) is a pregnancy-specific disease that causes maternal symptoms such as high blood pressure and adverse pregnancy outcomes. 2-methoxyestradiol (2-MeO-E2), an endogenous metabolite of 17ß-estradiol (E2) formed by Catechol-O-Methyltransferase (COMT), plays an important role in pregnancy. Our earlier studies have shown that polyphenols present in coffee can inhibit COMT activity, which may inhibit the formation of 2-MeO-E2 and contribute to PE. Therefore, the current study aims to investigate the possible effect and mechanism of coffee intake during pregnancy on PE in SD rats. Coffee is administered with or without cotreatment of 2-MeO-E2 to pregnant rats from the10th to the18th day of pregnancy. The results show that pregnant rats with coffee intake had prominent fetal growth restriction, hypertension and proteinuria, which can be ameliorated by co-treatment of 2-MeO-E2. In addition, coffee treatment leads to significantly decreased serum 2-MeO-E2. Therefore, the PE symptoms induced by coffee treatment is probably mediated by decreased 2-MeO-E2. Our findings provide new mechanistic insight into how coffee intake could lead to increased risk of PE, and demonstrate the effectiveness of 2-MeO-E2 supplementation as a potential therapeutic agent for PE.

18F-FDG PET/CT metabolic parameters can semi-quantitatively evaluate the nature of the heart and pericardial masses: a retrospective study.

The objective of this study was to evaluate semi-quantitatively the diagnostic performance of PET/CT metabolic parameters in differentiating benign or malignant cardiac or pericardial masses. A total of forty-one patients with newly diagnosed cardiac/pericardial masses who underwent 18F-FDG PET/CT were recruited. PET/CT metabolic parameters including the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), total lesion glycolysis (TLG), tumor metabolic volume (MTV), the maximum tumor-to-mediastinal background ratio (TMR) and the maximum tumor-to-liver background ratio (TLR) is measured or calculated to evaluate the benign or malignant nature of cardiac/pericardial masses. Compared with benign cardiac/pericardial lesions, cardiac/pericardial malignancies had higher SUVmax, SUVmean, TLG, MTV, TMR, and TLR. All these PET/CT metabolic parameters showed high diagnostic performance in semi-quantitative evaluation of benign or malignant cardiac or pericardial masses, and SUVmean and MTV had the highest diagnostic accuracy. Therefore, PET/CT metabolic parameters can semi-quantitatively evaluate the benign or malignant cardiac/pericardial masses.

CT, MRI, and PET/CT imaging features of thoracic spine epithelioid hemangioma: a retrospective observational study.

Introduction: Epithelioid hemangioma (EH) is an intermediate locally aggressive tumor that consists of epithelioid cells and endothelial cell differentiation, which can occur at any age, but is most common between the ages of 30 and 40 years. EH in the thoracic spine is rare, and accurate diagnosis is critical to treatment planning. Our aim was to explore the imaging and clinical data of thoracic spine EH to improve the understanding of this rare disease. Methods: From January 1, 2018 to June 30, 2023, a database of thoracic spine masses was retrospectively reviewed. Five patients with histologically proven thoracic spine EH and complete imaging available were identified and analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were evaluated separately by two radiologists with more than 10 years of experience. Positron emission tomography (PET)/CT was conducted by two nuclear medicine diagnostic technologists with at least 5 years of experience. Results: The patients included three male and two female patients aged 23 to 56 years (mean age was 38.4 ± 14.3 years). All patients underwent CT, MRI, and 18F-FDG PET/CT examination before treatment. Four patients were limited to one vertebral involvement, only one patient had multiple vertebral involvement, and all tumors involved the accessories, including one involving the posterior ribs. The maximum diameter of the tumor ranged from 2.7 to 4.3. Conclusions: CT, MRI, and 18F-FDG PET/CT findings of thoracic spine EH have certain characteristics, and understanding these imaging findings will help to obtain accurate diagnosis before surgery.

Metagenomic analysis reveals the mechanisms of biochar supported nano zero-valent iron in two-phase anaerobic digestion of food waste: microbial community, CAZmey, functional genes and antibiotic resistance genes.

The mechanisms of biochar supported nano zero-valent iron (BC/nZVI) on two-phase anaerobic digestion of food waste were investigated. Results indicated that the performance of both acidogenic phase and methanogenic phase was effectively facilitated. BC/nZVI with the amount of 120 mg/L increased methane production by 32.21%. In addition, BC/nZVI facilitated direct interspecies electron transfer (DIET) between Geobacter and methanogens. Further analysis showed that BC/nZVI increased the abundance of most CAZymes in acidogenic phase. The study also found that BC/nZVI had positive effects on metabolic pathways and related functional genes. The abundances of acdA and ackA in acidogenic phase were increased by 151.75% and 36.26%, respectively, and the abundances of pilA and TorZ associated with DIET were also increased. Furthermore, BC/nZVI mainly removed IMP-12, CAU-1, cmeB, ErmR, MexW, ErmG, Bla2, vgaD, MuxA, and cpxA from this system, and reduced the antibiotic resistance genes for antibiotic inactivation resistance mechanisms.

The efficacy of adjuvant chemotherapy in patients with different midpoint-radiotherapy Epstein-Barr virus DNA plasma loads.

OBJECTIVES: This study aimed to evaluate the efficacy of adjuvant chemotherapy (AC) in patients with different midpoint-radiotherapy (mid-RT) Epstein-Barr virus (EBV) DNA plasma loads for locoregionally advanced nasopharyngeal carcinoma (NPC), and to provide decision-making regarding the use of AC. MATERIALS AND METHODS: A total of 675 consecutive patients diagnosed with stage III-IVa NPC were enrolled in this study. All patients underwent concurrent chemoradiotherapy (CCRT), either with or without induction chemotherapy or AC, or a combination of both. The primary endpoint of this study was progression-free survival (PFS). RESULTS: Among the 675 enrolled patients, 248 (36.7 %) received AC and 427 (63.3 %) were only observed after CCRT. In total, 149 (22.1 %) patients had detectable mid-RT EBV DNA levels, whereas 526 (77.9 %) had undetectable mid-RT EBV DNA levels. Patients with detectable mid-RT EBV DNA had worse 5-year PFS than those with undetectable mid-RT EBV DNA (74.8 % vs. 81.9 %, P = 0.045). AC group showed significantly better 5-year PFS than observation in patients with detectable mid-RT EBV DNA (82.8 % vs. 66.8 %; HR, 0.480; 95 % CI 0.250-0.919, P = 0.027). Multivariate analyses demonstrated that the treatment methods (AC vs. observation) were independent prognostic factors for PFS (HR, 0.37; 95 % CI 0.19-0.74, P = 0.005). However, in patients with undetectable mid-RT EBV DNA (5-year PFS: HR 0.873, 95 % CI 0.565-1.349, P = 0.52), AC group showed no survival benefit for observation. CONCLUSION: AC could reduce the risk of disease progression compared to observation in patients with detectable mid-RT EBV DNA. Our findings suggest that AC is effective in patients at a high risk of treatment failure.

GDF6 in gastric cancer upregulated by helicobacter pylori induces epithelial-mesenchymal translation via the TGF-ß/SMAD3 signaling pathway.

OBJECTIVE: To investigate the association between Helicobacter pylori infection and GDF6 expression in gastric cancer patients, and to determine its influence on prognosis and resistance to capecitabine. METHODS: Tumor and adjacent non-tumor tissues were collected from 148 gastric cancer patients who underwent surgery in our department from October 2019 to June 2022. Of these patients, 78 tested positive for Helicobacter pylori and 70 tested negative. Hematoxylin-eosin (HE) and immunofluorescence staining were utilized to quantify GDF6 expression in cancerous and adjacent tissues. Patient prognosis was monitored via follow-up. Western blotting analyzed GDF6 expression in common gastric cancer cell lines. HGC27 cells exhibiting high GDF6 expression and BGC823 cells with low expression were used to create GDF6-silenced and overexpressed cell lines. The impact of GDF6 on the proliferation, migration, invasion, and cloning abilities of gastric cancer cells was evaluated using the CCK-8 assay, scratch test, Transwell assay, and plate colony formation assay. Fluorescent quantitative PCR and Western blotting assessed the effects of GDF6 levels on epithelial-mesenchymal transition (EMT) and tumor cell stemness. RESULTS: GDF6 expression in gastric cancer tissues was significantly correlated with cancer grading and staging (P<0.05). Helicobacter pylori-positive tissues exhibited significantly higher GDF6 expression levels than negative samples (P<0.05). Kaplan-Meier survival analysis indicated that high GDF6 expression was associated with poor survival prognosis. Overexpressed GDF6 enhanced the proliferation, migration, and invasion abilities of gastric cancer cells, while silencing GDF6 yielded opposite results. Increased GDF6 expression upregulated TGF-ß expression and the phosphorylation levels of SMAD3, leading to an elevation in mesenchymal cell markers N-cadherin, vimentin, and a reduction in epithelial cell markers cytokeratins, E-cadherin. Moreover, high GDF6 levels contributed to increased resistance to capecitabine and enhanced the expression of tumor stem cell markers Nanog, Sox-2, Oct-4, CD44, amplifying tumor cell stemness. CONCLUSION: Helicobacter pylori infection is associated with increased GDF6 expression in gastric cancer tissue, correlating with poor survival prognosis. Elevated GDF6 expression promotes the proliferation, migration, and invasion abilities of gastric cancer cells, facilitates EMT via the TGF-ß/SMAD3 pathway, and intensifies cell stemness and capecitabine resistance. Consequently, GDF6 presents itself as a potential new target for gastric cancer treatment. DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Suppressing Wnt signaling of the blood‒tumor barrier to intensify drug delivery and inhibit lipogenesis of brain metastases.

Lipogenesis is often highly upregulated in breast cancer brain metastases to adapt to intracranial low lipid microenvironments. Lipase inhibitors hold therapeutic potential but their intra-tumoral distribution is often blocked by the blood‒tumor barrier (BTB). BTB activates its Wnt signaling to maintain barrier properties, e.g., Mfsd2a-mediated BTB low transcytosis. Here, we reported VCAM-1-targeting nano-wogonin (W@V-NPs) as an adjuvant of nano-orlistat (O@V-NPs) to intensify drug delivery and inhibit lipogenesis of brain metastases. W@V-NPs were proven to be able to inactivate BTB Wnt signaling, downregulate BTB Mfsd2a, accelerate BTB vesicular transport, and enhance tumor accumulation of O@V-NPs. With the ability to specifically kill cancer cells in a lipid-deprived environment with IC50 at 48 ng/mL, W@V-NPs plus O@V-NPs inhibited the progression of brain metastases with prolonged survival of model mice. The combination did not induce brain edema, cognitive impairment, and systemic toxicity in healthy mice. Targeting Wnt signaling could safely modulate the BTB to improve drug delivery and metabolic therapy against brain metastases.

Differentiating Benign From Malignant Ovarian Masses With Solid Components: Diagnostic Performance of CEUS Combined With IOTA Simple Rules and O-RADS.

OBJECTIVE: This study aimed to apply the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR), the Ovarian-Adnexal Reporting and Data System (O-RADS) and contrast-enhanced ultrasound (CEUS) in an identical cohort of Chinese patients and to analyze their performance in discrimination of ovarian masses with solid components. METHODS: This was a two-center retrospective study that included a total of 94 ovarian lesions in 86 women enrolled from January 2018 to February 2023. The lesions were classified by using the IOTA terminology and CEUS was performed for the lesions exhibiting solid components on ultrasonography, IOTA SR and O-RADS were applied, and CEUS images were analyzed retrospectively. We assessed the time to wash-in, time to peak intensity (PI), PI compared to myometrium, and time to wash-out, and observed statistically significant differences between benign and malignant lesions in the first three parameters. CEUS characteristics were employed to determine CEUS scores for benign (score 0) and malignant (score 3) lesions. Subsequently, the lesions were reassessed based on the IOTA SR and O-RADS classifications and CEUS scores. The sensitivity, specificity, and area under the receiver-operating-characteristics curve (AUC) of the different models were also determined. RESULTS: Among the 94 ovarian lesions, 46 (48.9%) were benign and 48 (51.1%) were malignant. It was found that in the 60 lesions to which the SR could be applied, the sensitivity, specificity, and AUC was 0.900, 0.667, and 0.783, respectively. The sensitivity, specificity, and AUC of O-RADS was observed to be 1.000, 0.283 and 0.641, respectively. When SR and O-RADS were combined with CEUS, their sensitivity, specificity, and AUC values were increased to 0.917, 0.891, 0.904, and 0.958, 0.783, 0.871, respectively. CONCLUSION: IOTA SR and O-RADS exhibited relatively low specificity in differentiating malignant from benign ovarian lesions with the solid components, and their diagnostic performance can be significantly improved when combined with CEUS.

Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis.

Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as a glucose-lowering and weight loss medication due to its effects on energy metabolism. In heart failure, energy production is impaired due to altered mitochondrial function and increased glycolysis. However, the impact of semaglutide on cardiomyocyte metabolism under pressure overload remains unclear. Here we demonstrate that semaglutide improves cardiac function and reduces hypertrophy and fibrosis in a mouse model of pressure overload-induced heart failure. Semaglutide preserves mitochondrial structure and function under chronic stress. Metabolomics reveals that semaglutide reduces mitochondrial damage, lipid accumulation, and ATP deficiency by promoting pyruvate entry into the tricarboxylic acid cycle and increasing fatty acid oxidation. Transcriptional analysis shows that semaglutide regulates myocardial energy metabolism through the Creb5/NR4a1 axis in the PI3K/AKT pathway, reducing NR4a1 expression and its translocation to mitochondria. NR4a1 knockdown ameliorates mitochondrial dysfunction and abnormal glucose and lipid metabolism in the heart. These findings suggest that semaglutide may be a therapeutic agent for improving cardiac remodeling by modulating energy metabolism.

Flagellimonas halotolerans sp. nov., a novel bacterium isolated from the South China Sea.

Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C), and in the presence of 0-10 % NaCl (w/v; optimum 3 %). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10 %) in both strains were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83 %), followed by Flagellimonas aurea BC31-1-A7T (98.62 %), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76 %) and F. aurea BC31-1-A7T (98.55 %). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).

Malignant Melanoma of the Sphenoid Sinus: Case Report and Literature Review.

Malignant melanoma originating from the sphenoid sinus is an extremely rare but aggressive tumor of the head and neck. A 57-year-old man had a 1 month history of headache, right trigeminal paresthesias, and upper lid ptosis. Magnetic resonance imaging showed a large mass in the right sphenoid sinus and an invasion of the right cavernous sinus and clivus. The patient underwent endoscopic endonasal transsphenoidal surgery, and pathologically revealed malignant melanoma. One month after the operation, the patient was treated with radiation therapy. Unfortunately, the patient died of distant metastasis 2 years later. Due to its rarity, there is still no effective treatment strategy and no way to assess the progression of malignant melanoma.

Multimodal imaging findings of primary liver clear cell carcinoma: a case presentation.

Primary clear cell carcinoma of liver (PCCCL) is a special and relatively rare subtype of hepatocellular carcinoma (HCC), which is more common in people over 50 years of age, with a preference for men and a history of hepatitis B or C and/or cirrhosis. Herein, we present a case of a 60-year-old woman who came to our hospital for medical help with right upper abdominal pain. The imaging examination showed a low-density mass in the right lobe of his liver. In contrast enhanced computed tomography (CT) or T1-weighted imaging, significant enhancement can appear around the tumor during the arterial phase, and over time, the degree of enhancement of the tumor gradually decreases. The lession showed obviously increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/CT. These imaging findings contribute to the diagnosis of PCCCL and differentiate it from other types of liver tumors.

Expression, characterization and antivascular activity of amino acid sequence repeating collagen hexadecapeptide.

Type V collagen is an essential component of the extracellular matrix (ECM), and its remodeling releases specific protein fragments that can specifically inhibit endothelial cell responses such as proliferation, migration, and invasion. In this study, we have successfully constructed two engineered strains of Pichia pastoris capable of producing recombinant collagen through a new genetic engineering approach. Through high-density fermentation, the expression of 1605 protein and 1610 protein could reach 2.72 g/L and 4.36 g/L. With the increase of repetition times, the yield also increased. Bioactivity analysis showed that recombinant collagen could block the angiogenic effect of FGF-2 on endothelial cells by eliminating FGF-2-induced endothelial cell migration and invasion. Collectively, the recombinant proteins we successfully expressed have a wide range of potential for inhibiting angiogenesis in the biomaterials and biomedical fields.

Discovery and characterization of novel ATP citrate lyase inhibitors from Acanthopanax senticosus (Rupr. & Maxim.) Harms.

ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism, and abnormally high expression of ACLY occurs in many diseases, including cancers, dyslipidemia and cardiovascular diseases. ACLY inhibitors are prospective treatments for these diseases. However, the scaffolds of ACLY inhibitors are insufficient with weak activity. The discovery of inhibitors with structural novelty and high activity continues to be a research hotpot. Acanthopanax senticosus (Rupr. & Maxim.) Harms is used for cardiovascular disease treatment, from which no ACLY inhibitors have ever been found. In this work, we discovered three novel ACLY inhibitors, and the most potent one was isochlorogenic acid C (ICC) with an IC50 value of 0.14 ± 0.04 µM. We found dicaffeoylquinic acids with ortho-dihydroxyphenyl groups were important features for inhibition by studying ten phenolic acids. We further investigated interactions between the highly active compound ICC and ACLY. Thermal shift assay revealed that ICC could directly bind to ACLY and improve its stability in the heating process. Enzymatic kinetic studies indicated ICC was a noncompetitive inhibitor of ACLY. Our work discovered novel ACLY inhibitors, provided valuable structure-activity patterns and deepened knowledge on the interactions between this targe tand its inhibitors.

Strong Protection by 4-Hydroxyestrone against Erastin-Induced Ferroptotic Cell Death in Estrogen Receptor-Negative Human Breast Cancer Cells: Evidence for Protein Disulfide Isomerase as a Mechanistic Target for Protection.

Ferroptosis is a recently identified form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Recent studies have demonstrated that protein disulfide isomerase (PDI) is an important mediator of chemically induced ferroptosis and also a new target for protection against ferroptosis-associated cell death. In the present study, we identified that 4-hydroxyestrone (4-OH-E1), a metabolic derivative of endogenous estrogen, is a potent small-molecule inhibitor of PDI, and can strongly protect against chemically induced ferroptotic cell death in the estrogen receptor-negative MDA-MB-231 human breast cancer cells. Pull-down and CETSA assays demonstrated that 4-OH-E1 can directly bind to PDI both in vitro and in intact cells. Computational modeling analysis revealed that 4-OH-E1 forms two hydrogen bonds with PDI His256, which is essential for its binding interaction and thus inhibition of PDI's catalytic activity. Additionally, PDI knockdown attenuates the protective effect of 4-OH-E1 as well as cystamine (a known PDI inhibitor) against chemically induced ferroptosis in human breast cancer cells. Importantly, inhibition of PDI by 4-OH-E1 and cystamine or PDI knockdown by siRNAs each markedly reduces iNOS activity and NO accumulation, which has recently been demonstrated to play an important role in erastin-induced ferroptosis. In conclusion, this study demonstrates that 4-OH-E1 is a novel inhibitor of PDI and can strongly inhibit ferroptosis in human breast cancer cells in an estrogen receptor-independent manner. The mechanistic understanding gained from the present study may also aid in understanding the estrogen receptor-independent cytoprotective actions of endogenous estrogen metabolites in many noncancer cell types.

Case report: detection of multiple sporadic gastrointestinal stromal tumors by dual-time 18 F-FDG PET/CT.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors affecting the gastrointestinal tract. Typically, GISTs are solitary; however, in rare cases, they may be multiple and appear in one or more organs. Multiple GISTs can appear in familial GISTs, children, or certain tumor syndromes such as neurofibromatosis type 1, Carney syndrome, and Carney-Stratakis syndrome. However, the diagnosis of primary multiple sporadic GISTs is often more difficult than that of these diseases. Herein, we report a case of multiple primary sporadic GISTs in a 64-year-old man, affecting the abdominal cavity and retroperitoneum, as identified through dual-time point positron emission tomography (PET) with 18F-labeled fluoro-2-deoxyglucose (18F-FDG) and computed tomography (18F-FDG PET/CT). Notably, the dual-time-point PET/CT revealed the migration of masses near the lower abdomen into the abdominal cavity. Furthermore, a significant increase in radioactive uptake of the mass 3 h after 18F-FDG injection compared with that 1 h after injection may be an important cue for its diagnosis.

Phytochemical Profiling and Biological Activities of Pericarps and Seeds Reveal the Controversy on "Enucleation" or "Nucleus-Retaining" of Cornus officinalis Fruits.

The fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, α-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better α-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.

miRNA-383-5p Regulated Migration and Invasion of Tumor Cells by Inhibiting NCKAP1 Expression in Gastric Cancer.

Gastric cancer (GC) is the second deadliest disease in Asia, so it is crucial to find its promising therapeutic targets. The expression profile data of miR383-5p in the Cancer Genome Atlas (TCGA) were analyzed. The expression levels of miR383-5p in the collected clinical tissue samples and peripheral blood samples were examined by qPCR, and the relationship between its expression and the clinical data of patients was evaluated. MiR383-5p was overexpressed in the AGS cells, and cell biology assays, such as Transwell, were performed to detect the cell proliferation, migration, invasion and other cell biology abilities of miR383-5p. Target prediction and dual luciferase reporter gene assay were performed to find and validate the target genes of miR383-5p. The expression and activity of MMP and related proteins after overexpression of miR383-5p and NCKAP1 were detected by WB and gelatin zymography assay. The expression of miR383-5p was down-regulated in GC tissues, and its low expression was associated with lymph node metastasis. Restoration of miR383-5p expression in GC cells can inhibit the invasion and migration abilities of GC cells. MiR383-5p negatively regulated NCKAP1 through direct interaction with the 3'UTR sequence of NCKAP1. The overexpression of NCKAP1 can improve the migration and invasion abilities of GC cells, whereas overexpression of miR383-5p can inhibit growth of the aforementioned abilities of GC cells induced by NCKAP1 overexpression. The overexpression of NCKAP1 can increase the expression level and activity of MMP2, while the overexpression of miR383-5p can inhibit the increase of MMP2 expression level and activity in GC cells induced by NCKAP1 overexpression. NCKAP1 is a target gene of miR383-5p, and miR383-5p could be a valuable therapeutic target for stomach adenocarcinoma.

18F-FDG PET/CT revealed sporadic schwannomatosis involving the lumbar spinal canal and both lower limbs: a case report.

Schwannomatosis is a rare autosomal dominant hereditary syndrome disease characterized by multiple schwannomas throughout the body, without bilateral vestibular schwannoma or dermal schwannoma. The most common location of schwannomatosis is the head and neck, as well as the limbs, while multiple schwannomas in the lumbosacral canal and lower extremities are relatively rare. In this study, we report a 79-year-old woman diagnosed with schwannomatosis. MRI and contrast-enhanced imaging revealed multiple schwannomas in both lower extremities. An 18F-FDG PET/CT examination revealed that in addition to multiple tumors with increased 18F-FDG uptake in both lower extremities, there was also an increased 18F-FDG uptake in a mass in the lumbosacral canal. These masses were confirmed to be schwannomas by pathology after surgery or biopsy. 18F-FDG PET/CT findings of schwannomas were correlated with MRI and pathological components. Antoni A area rich in tumor cells showed significant enhancement on contrast-enhanced T1WI, and PET/CT showed increased uptake of 18F-FDG in the corresponding area, while Antoni B region rich in mucus showed low enhancement on contrast-enhanced T1WI, accompanied by a mildly increased 18F-FDG uptake.

Synthesis, characterization and in vitro antiproliferative effects of isosteviol derivatives.

Nineteen isosteviol derivatives were designed and synthesized by C-16, C-19 and D-ring modifications of isosteviol. These compounds were screened for their cytotoxic activities against Hela and A549 cells in vitro. Among them, the inhibitory effect of compounds 3b and 16 on Hela cells was comparable to that of the positive control gefitinib, and the compounds 3b (IC50=7.84 ± 0.84 µM) and 7a (IC50=6.89 ± 0.33 µM) exhibited significant cytotoxicity superior to gefitinib (IC50=11.02 ± 3.27 µM) against A549 cells.